Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

Esteban A Lopera-Maya; Alexander Kurilshikov; Adriaan van der Graaf; Shixian Hu; Lifelines Cohort Study; Sergio Andreu-Sánchez; Lianmin Chen; Arnau Vich Vila; Ranko Gacesa; Trishla Sinha; Valerie Collij; Marjolein A Y Klaassen; Laura A Bolte; Milla F Brandao Gois; Pieter B T Neerincx; Morris A Swertz; Hermie J M Harmsen; Cisca Wijmenga; Jingyuan Fu; Rinse K Weersma; Alexandra Zhernakova; Serena Sanna

doi:10.1038/s41588-021-00992-y

Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

Esteban A Lopera-Maya, Alexander Kurilshikov, Adriaan van der Graaf, Shixian Hu, Lifelines Cohort Study, Sergio Andreu-Sánchez, Lianmin Chen, Arnau Vich Vila, Ranko Gacesa, Trishla Sinha, Valerie Collij, Marjolein A Y Klaassen, Laura A Bolte, Milla F Brandao Gois, Pieter B T Neerincx, Morris A Swertz, Hermie J M Harmsen, Cisca Wijmenga, Jingyuan Fu, Rinse K WeersmaAlexandra Zhernakova^*, Serena Sanna^*

^*Corresponding author for this work

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Abstract

Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.

Original language	English
Pages (from-to)	143-151
Number of pages	9
Journal	Nature genetics
Volume	54
Early online date	3-Feb-2022
DOIs	https://doi.org/10.1038/s41588-021-00992-y
Publication status	Published - Feb-2022

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Author Correction: Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project (Nature Genetics, (2022), 54, 2, (143-151), 10.1038/s41588-021-00992-y)
Lifelines Cohort Study, Lopera-Maya, E. A., Kurilshikov, A., van der Graaf, A., Hu, S., Andreu-Sánchez, S., Chen, L., Vila, A. V., Gacesa, R., Sinha, T., Collij, V., Klaassen, M. A. Y., Bolte, L. A., Gois, M. F. B., Neerincx, P. B. T., Swertz, M. A., Harmsen, H. J. M., Wijmenga, C., Fu, J. & Weersma, R. K. & 2 others, Zhernakova, A. & Sanna, S., 1-Sept-2022, In: Nature genetics. 54, 9, p. 1448 1 p.
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7 Citations (Scopus)

Il genoma potrebbe influenzare il microbioma intestinale. Lo studio
Sanna, S.
07/02/2022
1 item of Media coverage
Press/Media: Research › Popular
Host Genetics Affect Makeup of Gut Microbiome, With Influence From Diet, Studies Find
Sanna, S.
04/02/2022
1 item of Media coverage
Press/Media: Research › Popular

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Lopera-Maya, E. A., Kurilshikov, A., van der Graaf, A., Hu, S., Lifelines Cohort Study, Andreu-Sánchez, S., Chen, L., Vila, A. V., Gacesa, R., Sinha, T., Collij, V., Klaassen, M. A. Y., Bolte, L. A., Brandao Gois, M. F., Neerincx, P. B. T., Swertz, M. A., Harmsen, H. J. M., Wijmenga, C., Fu, J., ... Sanna, S. (2022). Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project. Nature genetics, 54, 143-151. https://doi.org/10.1038/s41588-021-00992-y

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title = "Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project",

abstract = "Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.",

author = "Lopera-Maya, {Esteban A} and Alexander Kurilshikov and {van der Graaf}, Adriaan and Shixian Hu and {Lifelines Cohort Study} and Sergio Andreu-S{\'a}nchez and Lianmin Chen and Vila, {Arnau Vich} and Ranko Gacesa and Trishla Sinha and Valerie Collij and Klaassen, {Marjolein A Y} and Bolte, {Laura A} and {Brandao Gois}, {Milla F} and Neerincx, {Pieter B T} and Swertz, {Morris A} and Harmsen, {Hermie J M} and Cisca Wijmenga and Jingyuan Fu and Weersma, {Rinse K} and Alexandra Zhernakova and Serena Sanna and Patrick Deelen and Lude Franke and Kuivenhoven, {Jan Albert} and Nolte, {Ilja M.} and Harold Snieder and Vonk, {Judith M.}",

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month = feb,

doi = "10.1038/s41588-021-00992-y",

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volume = "54",

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Lopera-Maya, EA, Kurilshikov, A , van der Graaf, A, Hu, S, Lifelines Cohort Study, Andreu-Sánchez, S, Chen, L, Vila, AV, Gacesa, R , Sinha, T , Collij, V , Klaassen, MAY , Bolte, LA , Brandao Gois, MF , Neerincx, PBT , Swertz, MA , Harmsen, HJM , Wijmenga, C , Fu, J , Weersma, RK , Zhernakova, A & Sanna, S 2022, 'Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project', Nature genetics, vol. 54, pp. 143-151. https://doi.org/10.1038/s41588-021-00992-y

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T1 - Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

AU - Lopera-Maya, Esteban A

AU - Kurilshikov, Alexander

AU - van der Graaf, Adriaan

AU - Hu, Shixian

AU - Lifelines Cohort Study

AU - Andreu-Sánchez, Sergio

AU - Chen, Lianmin

AU - Vila, Arnau Vich

AU - Gacesa, Ranko

AU - Sinha, Trishla

AU - Collij, Valerie

AU - Klaassen, Marjolein A Y

AU - Bolte, Laura A

AU - Brandao Gois, Milla F

AU - Neerincx, Pieter B T

AU - Swertz, Morris A

AU - Harmsen, Hermie J M

AU - Wijmenga, Cisca

AU - Fu, Jingyuan

AU - Weersma, Rinse K

AU - Zhernakova, Alexandra

AU - Sanna, Serena

AU - Deelen, Patrick

AU - Franke, Lude

AU - Kuivenhoven, Jan Albert

AU - Nolte, Ilja M.

AU - Snieder, Harold

AU - Vonk, Judith M.

PY - 2022/2

Y1 - 2022/2

N2 - Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.

AB - Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.

U2 - 10.1038/s41588-021-00992-y

DO - 10.1038/s41588-021-00992-y

M3 - Article

C2 - 35115690

SN - 1061-4036

VL - 54

SP - 143

EP - 151

JO - Nature genetics

JF - Nature genetics

ER -

Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

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Author Correction: Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project (Nature Genetics, (2022), 54, 2, (143-151), 10.1038/s41588-021-00992-y)

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Il genoma potrebbe influenzare il microbioma intestinale. Lo studio

Host Genetics Affect Makeup of Gut Microbiome, With Influence From Diet, Studies Find

Cite this